UConn Center on Aging

Research doesn’t stop when we report it. Here are updates on past UConn Health Journal stories:

Glycogen Storage Disease

The world’s first gene therapy clinical trial for Glycogen Storage Disease (GSD) Type Ia is expected to start this year, hosted by the GSD Program at Connecticut Children’s Medical Center and UConn Health, under the direction of Dr. David Weinstein. The FDA–approved trials will be done in conjunction with biopharmaceutical company Ultragenyx.

Advancing Surgical Care for Older Adults

UConn John Dempsey Hospital will be one of seven U.S. hospitals to pilot-test newly developed guidelines for improving the quality of surgical care for older adults for the American College of Surgeons’ Coalition for Quality in Geriatric Surgery (CQGS), the American Geriatric Society, and the John A. Hartford Foundation.

Detecting Hearing Loss

Findings presented at the 53rd American Neurotology Society annual spring meeting reveal the first potential biomarker for noise-induced hearing loss. A collaborative study by UConn Health and Sensorion showed changing levels of prestin, an outer hair cell protein, in the blood correlated with the severity of hearing loss.

Breast Health

UConn Health assistant professor and breast surgeon Dr. Christina Stevenson has begun providing breast health education in hair salons, funded by the Connecticut Breast Health Initiative. The program aims to reach women in Hartford County who may be at risk for late- stage diagnosis of breast cancer due to health care access barriers.

Skin Cancer Screening

Up to 60 percent of UConn Health patients with a suspicious skin lesion or mole can now avoid invasive biopsies thanks to confocal microscopy technology, according to dermatologist Dr. Jane Grant-Kels. The technology uses a painless laser light to see skin cells on a cellular level and help doctors identify skin cancers, including melanoma.

Cooling Cap Therapy

Marisa Dolce, a Carole and Ray Neag Comprehensive Cancer Center breast cancer patient, reported keeping 70 percent of her hair as the first UConn Health patient to use optional scalp-cooling technology while undergoing chemotherapy. UConn Health is the only Connecticut institution outside Fairfield County to offer the FDA-approved DigniCap.

Research doesn’t stop when we report it. Here are updates on past UConn Health Journal stories:

Longevity Indicators

A new large-scale international study published in the journal Aging has expanded the number of genetic markers known to be associated with exceptional longevity from 8 to 25. Researchers at UConn, the University of Exeter, University of Wisconsin, and University of Iowa studied 389,166 volunteers who took part in U.K. Biobank, identifying genes that could one day be targeted to help prolong human life.

Health Disparities Institute

Wizdom Powell, Ph.D., associate professor of psychiatry, is the new director of the Health Disparities Institute at UConn Health. Powell’s focus in the eradication of health inequities is improving men’s mental health awareness, resources, and services. As chair of the American Psychological Association’s Working Group on Health Disparities in Boys and Men, Powell testified Jan. 30 to the Congressional Briefing on Men’s Mental Health in Washington, D.C., and proposed policy solutions to create a more supportive social climate for men suffering from depression.

Research doesn’t stop when we report it. Here are updates on past UConn Health Journal stories:

UConn Center on Aging

The UConn Center on Aging is one of 14 planned study sites for the TAME (Targeting Aging with Metformin) clinical trial led by Albert Einstein College of Medicine’s Dr. Nir Barzilai and colleagues from Wake Forest School of Medicine. The researchers hope to test the ability of diabetes drug metformin to slow development of aging-related conditions such as cancer, dementia, and cardiovascular diseases.

Childhood Anxiety Research

Anxiety in children may need to be treated as a chronic condition that requires regular follow-up, reported UConn Health psychologist Golda Ginsburg at this year’s Anxiety and Depression Association of America conference. The results are from a study that followed 488 children and adolescents with anxiety who were randomly assigned to get cognitive behavioral therapy (CBT), an antidepressant, CBT and an antidepressant, or a placebo. Remission rates five years after treatment were the same, no matter the treatment.

Two years ago, we published the first UConn Health Journal with the goal of giving physicians, dentists, and the public insight into the groundbreaking research and life-changing clinical care happening at UConn Health. As an academic medical center, UConn Health makes the discoveries that shape the future of health care. Our scientists work to understand medicine’s biggest mysteries, design new therapies and treatments, and turn laboratory breakthroughs into advances in patient care.

As our team collaborates to produce each issue, I constantly find myself in awe of everything that drives UConn Health’s innovations. Our stories can be heavy on science or heavy on heart, sometimes in the same issue. This spring, the story “Aches, Age, and Influenza” told of how UConn scientists’ findings in mice may help us prevent influenza-related muscle deterioration in the elderly. In the same edition, we got to know 11-year-old Alyssa Temkin, who since birth has struggled with an unforgiving, deadly disease for which a new UConn doctor is closing in on a cure.

Most of the time, though, our stories walk the line between the two. Because when it comes down to it, these advancements are based on science. But by definition, medical discoveries always impact real people. The mission of UConn Health Journal, like that of the UConn Health enterprise, is to translate that research: What does it mean for you? For your patients? For your loved ones?

In this issue, we’re exploring one topic from several angles. The brain has for centuries fascinated and perplexed. The more we learn about it, the more we find there is left to discover. At UConn, those who work with the brain range from a neurologist with a ringside seat to the evolution of concussion treatment to a radiologist and medical physicist who harnessed 3-D printing technology to give surgeons a practice brain for complicated procedures.

And please, let us know what you think and what else you’d like to read about. Email me anytime at julie.bartucca@uconn.edu.

With rising surgery demands among the growing population of older adults, the UConn Center on Aging and UConn John Dempsey Hospital are teaming up to identify older patients at the greatest risk of developing postoperative delirium in order to prevent it.

Patients with delirium have an altered level of alertness and are sometimes excessively drowsy, hyper-alert, or agitated. Although postoperative delirium is usually short-term, lasting hours or days, the brain may not recover for weeks or months in older adults. If the condition is not identified and addressed, delirium can lead to a decline in an older patient’s surgical recovery and cognitive and physical health, a need for caregiver or nursing home care, or potentially an increased risk of death.

“Our goal is to do everything in our power to screen older patients before surgery for delirium’s risk factors and to prevent it after surgery — or at least minimize its duration and effect,” says UConn Center on Aging’s Dr. Patrick Coll, who has been working closely with surgeons and anesthesiologists to modify preoperative delirium screening protocols at UConn Health. “All doctors really should be adding delirium-risk-factor screening to their preoperative evaluations for patients age 75 and above.”

Historically, surgery risk-prevention primarily focused on such areas as cardiac or pulmonary health. Last year, the American College of Surgeons and the American Geriatric Society issued new guidelines for optimal geriatric surgery patient management, which for the first time included screening for delirium risk before and after surgery.

“If a patient is deemed high-risk, the patient should have a geriatric assessment prior to surgery to help mitigate their risk and, after surgery, the hospital care team should plan to very closely monitor the patient,” said Coll.

The hospital care team can take simple, proactive steps to quickly reorient an older patient after surgery, Coll says. Even having a patient’s reading glasses and hearing aids readily available can make a big difference, as well as avoiding or limiting medications that can contribute to delirium, such as opioids.

With the help of aging expert Dr. Lavern Wright, UConn Health’s NICHE (Nurses Improving Care for Healthsystem Elders) program is expanding its scope to the surgical floors of the hospital to reduce older patients’ risk of delirium and other health complications. Further, all nurses now have access to the Confusion Assessment Method (CAM) tool and an electronic medical record order set to guide them in decreasing delirium’s impact.

In addition, Dr. Richard Fortinsky and his team are studying the effect of visiting clinical care teams at the homes of older adults with a history of delirium and other cognitive vulnerabilities to improve patient outcomes. This study, funded by the Patient-Centered Outcomes Research Institute, involves an in-home care program featuring a nurse practitioner who assesses older adults for delirium using a brief version of the CAM. The nurse practitioner also assesses for depression and dementia and teaches the patient and family members how to manage these conditions at home.

What We Know About Flu-Induced Muscle Loss and How to Prevent It

By Kim Krieger

Why does age impact flu-related muscle loss, and how can we prevent it? UConn Health researchers are on the case.

Muscle mystery

Most of us have seen it happen to a relative, friend, or patient. A formerly healthy senior gets a bad case of the flu. When they recover, they’re weak from muscle loss, sometimes permanently disabled. We don’t know exactly why the muscle loss happens, but UConn researchers are finding ways to prevent it.

It used to be that losing muscle was just a part of getting old. It’s considered normal aging. You can’t get a drug approved by the FDA to treat aging, because aging isn’t considered a disease. But influenza, the virus that causes the flu, is. If getting the flu speeds up muscle loss in seniors, then muscle loss is potentially preventable. But how could a virus that only infects the lungs cause muscle loss?

Wasting away

When immunologist Laura Haynes first came to UConn Health, she knew that when mice get the flu, they lose weight. In fact, that’s the way researchers can tell that a mouse has the virus. Some mice lose more, some less. Haynes’ work had previously shown that older mice with the flu not only get much sicker, but also lose more weight than younger mice. But as an immunologist, her research focused on how aging immune systems decline. Differences in weight loss were an afterthought. But when she sat down with Dr. George Kuchel, director of the UConn Center on Aging, they made the connection that weight loss might indicate future disability.

Haynes teamed up with kinesiologist Jenna Bartley to further investigate. They confirmed that a significant amount of the weight lost by mice infected with the flu was muscle. And older mice infected with influenza lost more muscle than younger mice, and continued to lose it over a longer period of time.

It’s really hard to improve elderly immune response. So if we can’t prevent them from getting the flu, maybe we could at least prevent muscle loss and future disability.

— Jenna Bartley, Kinesiologist, Department of Immunology

“In mice there are changes in gene expression in muscle during influenza infection. Genes that degrade muscle go up, genes that build muscle go down. But in young mice, the gene expression goes back to normal more quickly,” says Haynes. The older mice, on the other hand, had higher levels of inflammation, muscle wasting, and atrophy, and it all persisted longer.

Exacerbated muscle loss wasn’t the only problem experienced by the older mice recovering from the flu. They also moved less and took fewer, narrower steps. It was as if they had become frailer and more easily tired. Decreasing gait speed, or how fast someone walks, indicates increasing frailty in humans, and taking narrower steps also increases the risk of falling. [See ‘UConn Pilots Quick Gait-Speed Measurement’]

Haynes and Bartley’s research was the first that directly linked flu-induced inflammation in a controlled setting to muscle atrophy and functional impairment. It was published in the April 2016 issue of the journal Aging. But now that they knew flu really was causing muscle wasting, how could they stop it? Even yearly vaccination doesn’t provide 100-percent protection.

“It’s really hard to improve elderly immune response. So if we can’t prevent them from getting the flu, maybe we could at least prevent muscle loss and future disability,” says Bartley.

Stemming the tide

Haynes and Bartley suspected that influenza-induced inflammation was related to, and possibly the cause of, the destruction of muscle tissue in the elderly mice. They theorized that if they could stem the tide of inflammation in the body, they might prevent the muscle tissue from degrading so much. But there was a catch: inflammation helps mobilize the immune system. If you block inflammation totally, you block the body’s defense against the flu virus. So Haynes and Bartley needed a more subtle tool.

In mice there are changes in gene expression in muscle during influenza infection. Genes that degrade muscle go up, genes that build muscle go down. But in young mice, the gene expression goes back to normal more quickly.

— Laura Haynes, Immunologist, UConn Center on Aging

The first drugs Bartley and Haynes found that might be good candidates are COX-2 inhibitors. They’re non-steroidal anti-inflammatories, like aspirin and ibuprofen, but COX-2 inhibitors are very specific. They block just one molecule in the body’s web of inflammatory responses. Other researchers have shown that COX-2 inhibitors can slow muscle wasting in cancer patients. And most importantly, COX-2 inhibitors don’t seem to block the body’s antiviral immune reaction.

Haynes and Bartley are currently testing the COX-2 inhibitors to see if they prevent muscle loss in geriatric mice after the flu. They’re also testing whether improving immune memory of the flu in mice — that is, vaccinating them — protects them against muscle wasting.

Their work is intriguing, but Kuchel cautions that adult humans are more complicated than lab mice.

“Factors that may contribute to an older individual becoming more vulnerable to losing muscle function during or after flu infection are complex but may include a sedentary lifestyle, slow walking speed at baseline, low muscle mass, poor nutrition, plus chronic inflammation as a result of any number of chronic infections, being frail, etc.,” he says.

Bartley and Haynes agree. They’re applying for more grant money to explore how COX-2 inhibitors interact with other factors such as exercise. And they hope to eventually test muscle-protection strategies in people. Because while influenza is one of the most common serious infections in the elderly, it probably isn’t alone in causing muscle wasting.

“We’re trying to establish the relationship between any infection and inflammation, and how it leads to muscle loss and disability,” says Bartley. “Overall, we’re trying to help people get better and stay stronger for longer.”

Procedure spotlight

UConn Pilots Quick Gait-Speed Measurement

Gait speed — how fast you walk — is a good predictor of overall health. Many geriatricians consider it a “fifth vital sign” as important as body temperature, pulse, respiration rate, and blood pressure. A sudden slowdown may signal that a senior’s health is in decline. The Centers for Medicare and Medicaid Services is considering having doctors measure gait speed at every check-up. Yet, the gold standard of timing gait speed over a short distance using a stopwatch is inconvenient and prone to variability due to human error.

Now, researchers at UConn Health and the UConn School of Engineering have a better way. Investigators from the Center on Aging found that Radio Frequency ID (RFID) tags are an easy, almost foolproof way to measure gait speed. Over the summer they had a medical student fit 50 patients between the ages of 65 and 95 with an armband carrying an RFID tag, and then asked them to walk down the hall at their normal speed. Tag readers at either end of the hall detected the tag as the patient passed and automatically calculated how fast the person was walking.

A sudden slowdown in gait speed signals a senior’s health is in decline.

The patients didn’t mind the non-invasive process at all. The medical assistants said it was easy and wouldn’t add more than a few seconds to their task list. And if the tag readers are strategically placed, it could be even faster. For example, a medical assistant could hand the RFID tag to the patient in the waiting room and walk them to the exam room, passing the tag readers along the way.

“We want to be able to track someone’s usual gait speed over time. If someone comes back six months later and their usual gait speed has slowed considerably, this may signify an opportunity to intervene clinically to prevent further decline,” says Lisa Barry, a chronic disease epidemiologist at UConn Health. Barry says the gait speed measurements could also be used as an indicator of how well a patient is responding to rehabilitation and treatment following surgery or a serious illness. She and Dr. George Kuchel, director of the UConn Center on Aging, are currently looking at developing a commercial prototype so that doctors elsewhere can start using the technique to benefit their own patients.

‘Morrbid’ RNA Could Be Key to Asthma Treatment

Researchers have discovered a potential therapeutic target for inflammatory disorders that are characterized by abnormal myeloid cell lifespan, such as asthma, Churg-Strauss syndrome, and hypereosinophilic syndrome. Investigators including Adam Williams of UConn Health and The Jackson Laboratory named the novel long non-coding RNA ‘Morrbid’ (Myeloid RNA Regulator of Bim-Induced Death). They discovered that Morrbid tightly controls how long circulating myeloid cells live — which is key to maintaining the balance between fighting infection and exacerbating inflammation — by overriding a signaling mechanism that prevents premature immune cell death. In mice, deleting the gene helped protect them against inflammation and immunopathology. The findings were published online in Nature, Aug. 15, 2016.

Parents Living Longer is Good News for Offspring, Study Says

A new study led by the University of Exeter and co-authored by the UConn Center on Aging, among other international contributors, shows that how long a person’s parents live can help predict how long the offspring will live, and how healthy the child will be as he or she ages. The study of 186,000 participants, aged 55 to 73 years and followed for up to eight years, is the largest of its kind. It found that a person’s chance of survival increased by 17 percent for each decade that at least one parent lived beyond age 70, and that those with longer-lived parents had lower rates of heart disease and other circulatory conditions, as well as cancer. The study was published in the Journal of the American College of Cardiology, Aug. 15, 2016.

PRP Limits Ill Effects of Osteoarthritis Treatment

Giving platelet-rich plasma (PRP) to patients undergoing treatment for osteoarthritis may limit the negative effects of the drugs used to manage their symptoms, according to a new study led by Dr. Augustus Mazzocca, director of the UConn Musculoskeletal Institute, and the University of Pittsburgh Medical Center. Osteoarthritis is the most common chronic condition of the joints, causing pain, stiffness, and swelling in approximately 27 million Americans. Powerful anti-inflammatory medicines and local anesthetics relieve pain and improve range of motion, but can also lead to tissue degeneration. In the study, published in the August issue of The American Journal of Sports Medicine, researchers found combining PRP with these treatments significantly reduced their toxic effect on the cells and even improved their proliferation.

Bath Salts 101: Pharmacist Explains Party Drugs

Synthetic party drugs with dangerous hallucinogenic properties, such as those sold commercially as “bath salts,” continue to pose a significant public health risk around the country. C. Michael White — head of the Department of Pharmacy Practice in UConn’s School of Pharmacy — published a comprehensive review of synthetic cathinones in the June 2016 issue of The Journal of Clinical Pharmacology to help clinicians recognize signs of abuse and properly treat patients with adverse events, ranging from psychosis to heart disease, from the drugs. This is the third in a series of articles on drugs including molly/ecstasy and GHB that he wrote to support clinicians. He is currently working on an assessment of synthetic marijuana.

Researchers at UConn Health and Beth Israel Deaconess Medical Center have found that a blood test could make it easier to identify patients at risk for delirium, the sudden, acute state of confusion that most often affects older adults and incurs $6.9 billion in medical costs each year in the U.S. Their study, published online in The Journal of Gerontology: Medical Sciences, reports that elevated blood levels of specific proteins called cytokines can hint that a patient will develop delirium during a hospital stay.

If you do things such as improve a patient’s vision and hearing, reorient them to where they are regularly, promote restful sleep, increase mobility, and stop medications that could be making the delirium worse, all that can help.

— Dr. George Kuchel, director of the UConn Center on Aging

Dr. George Kuchel, director of the UConn Center on Aging and one of the authors of the study, says the suspected blood signature for delirium shows two cytokines at higher-than-normal levels in patients who develop delirium. Both cytokines are associated with inflammation.

Researchers don’t yet know exactly how inflammation and delirium are linked. The two cytokines the researchers saw in the blood signature, interleukin-6 and interleukin-2, can cause swelling of the membrane around the brain. Chronic stress from low-level illness can also elevate both cytokines and stress hormones such as cortisol, which over the long term can shrink part of the brain and perhaps increase an elderly person’s susceptibility to delirium.

Kuchel and his colleagues worked with patients who participated in the Successful Aging after Elective Surgery (SAGES) study to get a better handle on the relationship between inflammation and delirium. This large study, sponsored by the National Institute on Aging, has been following 566 surgical patients over the age of 70 for the past five years, with the goal of finding new approaches to prevent delirium and its long-term consequences in older adults.

The UConn study found that patients who developed delirium had higher levels of interleukin-2 than non-delirium patients at all times they were tested: before surgery, in the first two days afterward, and one month later.

This is the first study to look at cytokine levels in older surgical patients at several points in time, both before and after surgery. The results need to be replicated in other studies, but if they prove to be generally true, the blood signature could provide a quick way to alert doctors and nurses to seniors at higher risk of delirium. They can then take extra precautions to keep the patients oriented.

“If you do things such as improve a patient’s vision and hearing, reorient them to where they are regularly, promote restful sleep, increase mobility, and stop medications that could be making the delirium worse, all that can help,” says Kuchel.

Pharmacies advertising flu vaccinations in August and September are doing their elderly clients a disservice, say UConn Center on Aging researchers. The immunity they gain from vaccine in late summer may wane by the time flu season hits hard in late winter.

As summer temperatures peaked this August, pharmacies were already advertising the influenza vaccine. But if you thought that was too early to be getting a flu shot — you were right.

If you’re interested in volunteering for the study, contact Lisa Kenyon at the UConn Center on Aging at 860.679.3956.

“When adults get the vaccine in September, the peak effect wears off by late December. But flu season peaks in January and February,” warns Laura Haynes, an immunologist and gerontologist at UConn Health.

October or November is a much better time to get the vaccine. That way, you’re still protected when virus season is at its worst.

This is especially important for the elderly, who are at particular risk from flu. People over 65 are much more likely than younger adults to have serious complications or even die from a bout with the virus.

One way to better stimulate the immune response is to administer a high-dose vaccine, which contains four times as much flu antigen as the regular version. But the high-dose vaccine has stronger side effects, is more expensive, and may not be best for everyone.

Haynes and her colleagues at UConn Health, funded by a Program Project Grant from the National Institute on Aging, will run two studies this autumn to better understand older people’s responses to the regular flu vaccine and the high-dose version. The studies will look at how the immune system reacts to the flu vaccine, as well as how to identify patients who would benefit from the high-dose version.